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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2020; 78(12): 805-810
DOI: 10.1590/0004-282X20200186
Seção

Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature

Encefalomielite disseminada aguda associada a COVID-19: relato de dois casos e revisão de literatura
Cesar Castello Branco Lopes 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Sonia Maria Dozzi Brucki 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
2   Hospital Santa Marcelina, Departamento de Neurologia, São Paulo SP, Brazil.
,
Carlos Eduardo Borges Passos  Neto
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Luiza Alves Corazza 
2   Hospital Santa Marcelina, Departamento de Neurologia, São Paulo SP, Brazil.
,
José Pedro Soares Baima 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Matheus Dalben Fiorentino 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
João Fellipe Santos Tatsch 
2   Hospital Santa Marcelina, Departamento de Neurologia, São Paulo SP, Brazil.
,
Maria da Graça Morais Martin 
3   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto de Radiologia, São Paulo SP, Brazil.
,
Leandro Tavares Lucato 
3   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto de Radiologia, São Paulo SP, Brazil.
,
Hélio Rodrigues Gomes 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Maria Sheila Guimarães Rocha 
2   Hospital Santa Marcelina, Departamento de Neurologia, São Paulo SP, Brazil.
,
Ida Fortini 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Ricardo Nitrini 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
,
Luiz H. Castro 
1   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil.
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ABSTRACT

Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

RESUMO

Introdução: As manifestações neurológicas causadas pela COVID-19 ainda não estão completamente elucidadas. O comprometimento neurológico pode decorrer de um efeito viral direto em neurônios ou em células gliais, a efeito imunomediado em resposta à infecção viral, ou de um efeito secundário a estados de hipercoagulabilidade e danos endoteliais, assim como decorrente de complicações sistêmicas graves relacionadas a cuidados intensivos prolongados na unidade de terapia intensiva. Objetivo: Descrever dois pacientes com recuperação tardia do nível de consciência após a retirada da sedação associados à infecção grave pelo SARS-CoV-2, que apresentaram lesões multifocais de substância branca, compatíveis com o diagnóstico de encefalomielite disseminada aguda. Métodos: Estudo observacional, com relato de dois casos de infecção grave pela COVID-19, em dois hospitais terciários na cidade de São Paulo, Brasil. Resultados: Os pacientes foram submetidos à investigação sistêmica e neurológica para avaliação de estado alterado de consciência após retirada de sedação. A ressonância magnética de crânio evidenciou lesões multifocais no centro semioval, sugestivos de processo inflamatório desmielinizante. Análise liquórica evidenciou PCR negativo para SARS-CoV-2 em ambos os casos. Conclusão: Lesões multifocais de substância branca podem ocorrer em pacientes com COVID-19, possivelmente associadas a estados alterados de consciência. Estudos adicionais são necessários para determinar o processo fisiopatológico da infecção viral e dos estados inflamatórios e imunomediados na gênese das manifestações neurológicas causadas pela COVID-19.

Keywords:

Neurology - Coronavirus Infections - Encephalitis - Central Nervous System Infections - Demyelinating Diseases

Palavras-chave:

Neurologia - Infecções por Coronavírus - Encefalite - Infecções do Sistema Nervoso Central - Doenças Desmielinizantes

Author’s contributions:

All authors contributed to the study conception and design. Luiza Corazza, João Tatsch, Maria Rocha and Sonia Brucki contributed to the evaluation and data acquisition of patient 1. Cesar Lopes, Matheus Fiorentino, Carlos Neto, José Baima, Ida Fortini, Hélio Gomes, Ricardo Nitrini and Luiz Castro contributed to the evaluation and data acquisition patient 2. Maria Martin and Leandro Lucato contributed to interpretation and discussion of the neuroimaging findings. All authors contributed in writing the main manuscript, which was critically reviewed by all.




Publication History

Received: 27 August 2020

Accepted: 06 October 2020

Article published online:
07 June 2023

© 2020. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, et al. Neurological associations of COVID-19. Lancet Neurol. 2020 Jul;19(9):767-83. https://doi.org/10.1016/s1474-4422(20)30221-0
  • 2 Munhoz RP, Pedroso JL, Nascimento FA, Almeida SM, Barsottini OGP, Cardoso FEC, et al. Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arq Neuropsiquiatr. 2020 May;78(5):290-300. https://doi.org/10.1590/0004-282x20200051
  • 3 Zhang T, Rodricks MB, Hirsh E. COVID-19-associated acute disseminated encephalomyelitis: a case report. Neurocrit Care. 2020 AprOct; 1-7. https://doi.org/10.1007/s12028-020-01119-7
  • 4 Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020 Oct;143(10):3104-20. https://doi.org/10.1093/brain/awaa240
  • 5 Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Jun;382(23):2268-70. https://doi.org/10.1056/nejmc2008597
  • 6 Kandemirli SG, Dogan L, Sarikaya ZT, Kara S, Akinci C, Kaya D, et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection [published online ahead of print, 2020 May 8]. Radiology. 2020 May;297(1):E232-5.. https://doi.org/10.1148/radiol.2020201697
  • 7 McIntosh K, Becker WB, Chanock RM. Growth in suckling-mouse brain of “IBV-like” viruses from patients with upper respiratory tract disease. Proc Natl Acad Sci U S A. 1967 Oct;58(6):2268-73. https://doi.org/10.1073/pnas.58.6.2268
  • 8 Panciani PP, Saraceno G, Zanin L, Renisi G, Signorini L, Battaglia L, et al. SARS-CoV-2: “Three-steps” infection model and CSF diagnostic implication. Brain Behav Immun. 2020 Jul;87:128-9. https://doi.org/10.1016/j.bbi.2020.05.002
  • 9 Pohl D, Alper G, Van Haren K, Kornberg AJ, Lucchinetti CF, Tenembaum S, et al. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology. 2016 Aug;87(9 Suppl 2):S38-45. https://doi.org/10.1212/wnl.20200186202001862825
  • 10 Cole J, Evans E, Mwangi M, Mar S. Acute Disseminated Encephalomyelitis in Children: An Updated Review Based on Current Diagnostic Criteria. Pediatr Neurol. 2019 Jul;100:26-34. https://doi.org/10.1016/j.pediatrneurol.2019.06.017
  • 11 Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013 Apr;19(10):1261‐7. https://doi.org/10.1177/1352458513484547
  • 12 Ketelslegers IA, Visser IE, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ. Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children. Mult Scler. 2011 Dec;17(4):441-8. https://doi.org/10.1177/1352458510390068
  • 13 Kamr, W.H., Tantawy AM, Moustafa M, Adb-Elsalam OA. Acute disseminated encephalomyelitis: MR Diffusion weighted imaging: Potential diagnostic value and outcome predilection. The Egyptian Journal of Radiology and Nuclear Medicine, 2017 Mar;48(1):215-23. https://doi.org/10.1016/j.ejrnm.2017.01.004.
  • 14 Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004 Jan;113(1 Pt 1):e73‐6. https://doi.org/10.1542/peds.113.1.e73
  • 15 Arabi YM, Harthi A, Hussein J, Bouchama A, Johani S, Hajeer AH, et al. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection. 2015 Jan;43(4):495-501. https://doi.org/10.1007/s15010-015-0720-y
  • 16 Barac-Latas V, Suchanek G, Breitschopf H, Stuehler A, Wege H, Lassmann H. Patterns of oligodendrocyte pathology in coronavirus-induced subacute demyelinating encephalomyelitis in the Lewis rat. Glia. 1997 Dec;19(1):1‐12. https://doi.org/10.1002/(sici)1098-1136(199701)19:1%3C1::aid-glia1%3E3.0.co;2-5
  • 17 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar;395(10229):1033‐4. https://doi.org/10.1016/s0140-6736(20)30628-0
  • 18 Caso F, Costa L, Ruscitti P, Navarini L, Del Puente A, Giacomelli R, et al. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev. 2020 May;19(5):102524. https://doi.org/10.1016/j.autrev.2020.102524
  • 19 Murray RS, Cai GY, Hoel K, Zhang JY, Soike KF, Cabirac GF. Coronavirus infects and causes demyelination in primate central nervous system. Virology. 1992 May;188(1):274‐84. https://doi.org/10.1016/0042-6822(92)90757-G
  • 20 Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol. 2020 May;140(1):1-6. https://doi.org/10.1007/s00401-020-02166-2
  • 21 Novi G, Rossi T, Pedemonte E, Saitta L, Rolla C, Roccatagliata L, et al. Acute disseminated encephalomyelitis after SARS-CoV-2 infection. Neurol Neuroimmunol Neuroinflamm. 2020 Jun;7(5):e797. https://doi.org/10.1212/nxi.20200186202001860797
  • 22 Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M. COVID-19-associated acute disseminated encephalomyelitis (ADEM). J Neurol. 2020 May;267(10):2799-802. https://doi.org/10.1007/s00415-020-09951-9
  • 23 McCuddy M, Kelkar P, Zhao Y, Wicklund D. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series.2020 Sep-Oct;68(5):1192-5. https://doi.org/10.1101/2020.07.15.20126730.
  • 24 Marchioni E, Marinou-Aktipi K, Uggetti C, Bottanelli M, Pichiecchio A, Soragna D, et al. Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis. J Neurol. 2002 Jan;249(1):100-4. https://doi.org/10.1007/PL00007836